What role does the immune system play in fertility?
A pregnancy is a unique situation from an immunological point of view because the mother’s immune system has to ‘recognise’ an embryo with at least half of the antigens (proteins that the immune system recognises) are of paternal origin. To do this, a situation of inactivation or increased tolerance in the mother’s immune system occurs, so that the embryo’s placenta can invade the maternal uterus without rejection. Therefore, the embryo implantation process and the correct development of the pregnancy depend on a delicate balance that allows tolerance between two immunologically different individuals.
The immune system protects the body from foreign cells and diseases by means of different blood cells (white blood cells or leukocytes) and antibodies. They all react against viruses, bacteria, parasites or even altered cells such as cancerous cells, and are also responsible for attacking the body’s own organs, as in the case of autoimmune diseases, or for the rejection of organ transplants in some cases.
Recurrent implantation failure (absence of gestation after having performed at least 3 transfers of chromosomally normal embryos) or recurrent gestational losses (two or more miscarriages) are two situations with which we specialists in reproductive medicine frequently deal and which are especially frustrating when there is no known cause for the failure. Among the multiple causes that are being investigated in these cases, one of them is a possible alteration of the maternal immune system.
At present, the only immune disorder linked to a large percentage of reproductive failures is antiphospholipid syndrome. Together with embryonic chromosomal abnormalities, it is the only proven cause of repeated miscarriages. This disease is characterized by the presence in maternal blood of antibodies called antiphospholipids. These cause thrombotic phenomena (especially microthrombosis) at the placental leading to pregnancy loss. Treatment with low-dose acetylsalicylic acid and low molecular weight heparin at prophylactic doses has been shown to be effective in reducing the miscarriage risk.
The rest of the immune system disorders that could increase the risk of reproductive failure are currently under investigation. We are talking about anomalies in the way the cells of the maternal immune system act (T lymphocytes, Natural Killer cells, etc.), as well as certain genetic variants in these cells that could increase the risk of embryonic rejection (KIR-HLA-C system).
The treatments available are aimed at suspending or modulating the alterations in the immune system and other existing alterations. Among the drugs to which it is possible to resort, we have to highlight the use of corticoids, hydroxychloroquine, intravenous immunoglobulins, intralipids, immunosuppressive drugs… However, given that the evidence with the use of these drugs is within the field of research, and is very limited, and that they are drugs that are not free of side effects, their prescription should always be made in a clinical context by a specialist in reproductive medicine.
Other proposed strategies, especially in cases of incompatibility of the maternal KIR system with the HLA-C of the embryo, are single embryo transfer to reduce the risk of rejection by “stimulating” the maternal immune system as little as possible, and the selection of HLA C compatible donors in gamete donation treatments.
Research on the immune system and infertility has advanced, but it is still very scarce, creating results which, although they may be a starting point, do not constitute unquestionable scientific evidence, nor can their application in daily clinical practice be standardised.
Dr. Cristina García-Ajofrín, gynaecologist at Instituto Bernabeu